Multi-electrode molecular sensing devices and methods of making the same

ABSTRACT

A molecular sensor includes a substrate defining a substrate plane, and a plurality of pairs of electrode sheets above or below the substrate at an angle to the substrate plane. The molecular sensor further includes a plurality of inner dielectric sheets between each electrode sheet in each pair of electrode sheets of the plurality of pairs, and an outer dielectric sheet between each pair of electrode sheets of the plurality of pairs.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Non-Provisional patentapplication Ser. No. 15/728,412, filed Oct. 9, 2017, which is adivisional application of U.S. Non-Provisional patent application Ser.No. 15/220,307, filed Jul. 26, 2016, which issued as U.S. Pat. No.9,829,456 on Nov. 28, 2017, the disclosures of which are incorporatedherein by reference in their entirety.

FIELD

The present disclosure relates to nanofabrication and nanoelectronics.More particularly, the present disclosure relates to devices, and thefabrication of devices for sensing and analyzing molecules, includinggenome sequencing and DNA sequencing.

BACKGROUND

Molecular analysis has received an increasing amount of attention invarious fields such as precision medicine or nanotechnology. One exampleincludes the analysis of molecules for sequencing genomes. The seminalwork of Avery in 1946 demonstrated that DNA was the material thatdetermined traits of an organism. The molecular structure of DNA wasthen first described by Watson and Crick in 1953, for which theyreceived the 1962 Nobel Prize in Medicine. This work made it clear thatthe sequence of chemical letters (bases) of the DNA molecules encode thefundamental biological information. Since this discovery, there has beena concerted effort to develop means to actually experimentally measurethis sequence. The first method for systematically sequencing DNA wasintroduced by Sanger in 1978, for which he received the 1980 Nobel Prizein Chemistry.

A basic method for sequencing a genome was automated in a commercialinstrument platform in the late 1980's, which ultimately enabled thesequencing of the first human genome in 2001. This was the result of amassive public and private effort taking over a decade, at a cost ofbillions of dollars, and relying on the output of thousands of dedicatedDNA sequencing instruments. The success of this effort motivated thedevelopment of a number of “massively parallel” sequencing platformswith the goal of dramatically reducing the cost and time required tosequence a human genome. Such massively parallel sequencing platformsgenerally rely on processing millions to billions of sequencingreactions at the same time in highly miniaturized microfluidic formats.The first of these was invented and commercialized by Rothberg in 2005as the 454 platform, which achieved thousand fold reductions in cost andinstrument time. However, the 454 platform still required approximatelya million dollars and took over a month to sequence a genome.

The '454 platform was followed by a variety of other related techniquesand commercial platforms. This progress lead to the realization of thelong-sought “$1,000 genome” in 2014, in which the cost of sequencing ahuman genome at a service lab was reduced to approximately $1,000, andcould be performed in several days. However, the highly sophisticatedinstrument for this sequencing cost nearly one million dollars, and thedata was in the form of billions of short reads of approximately 100bases in length. The billions of short reads often further containederrors so the data required interpretation relative to a standardreference genome with each base being sequenced multiple times to assessa new individual genome.

Thus, further improvements in quality and accuracy of sequencing, aswell as reductions in cost and time are still needed. This is especiallytrue to make genome sequencing practical for widespread use in precisionmedicine, where it is desirable to sequence the genomes of millions ofindividuals with a clinical grade of quality.

While many DNA sequencing techniques utilize optical means withfluorescence reporters, such methods can be cumbersome, slow indetection speed, and difficult to mass produce to further reduce costs.Label-free DNA or genome sequencing approaches provide advantages of nothaving to use fluorescent type labeling processes and associated opticalsystems, especially when combined with electronic signal detection thatcan be achieved rapidly and in an inexpensive way.

In this regard, certain types of molecular electronic devices can detectsingle molecule, biomolecular analytes such as DNAs, RNAs, proteins, andnucleotides by measuring electronic signal changes when the analytemolecule is attached to a circuit. Such methods are label-free and thusavoid using complicated, bulky and expensive fluorescent type labelingapparatus.

While current molecular electronic devices can electronically measuremolecules for various applications, they lack the scalability andmanufacturability needed for rapidly sensing many analytes at a scale ofup to millions in a practical manner. Such highly scalable methods areparticularly important for DNA sequencing applications, which often needto analyze millions to billions of independent DNA molecules. Inaddition, the manufacture of current molecular electronic devices isgenerally costly due to the high level of precision needed.

BRIEF DESCRIPTION OF THE DRAWINGS

The features and advantages of the embodiments of the present disclosurewill become more apparent from the detailed description set forth belowwhen taken in conjunction with the drawings. The drawings and theassociated descriptions are provided to illustrate embodiments of thedisclosure and not to limit the scope of what is claimed.

FIG. 1A is a cross section view showing fabrication of a molecularsensor by sequentially depositing tri-layer thin film device stacksusing a low deposition angle and a sacrificial top layer according to anembodiment.

FIG. 1B is a cross section view showing further fabrication of themolecular sensor of FIG. 1A.

FIG. 1C is a cross section view of the molecular sensor of FIGS. 1A and1B after fabrication.

FIG. 2A is a cross section view showing fabrication of a molecularsensor by sequentially depositing tri-layer thin film device stacksusing a low deposition angle and detachable shades according to anembodiment.

FIG. 2B is a cross section view showing further fabrication of themolecular sensor of FIG. 2A.

FIG. 2C is a cross section view of the molecular sensor of FIGS. 2A and2B after fabrication.

FIG. 3 is a flowchart for a manufacturing process of the molecularsensor of FIG. 1C or FIG. 2C according to an embodiment utilizing lowincident angle oblique deposition.

FIG. 4A is a cross section view showing fabrication of a molecularsensor by sequentially depositing tri-layer thin film device stacksusing a high deposition angle according to an embodiment.

FIG. 4B is a cross section view of the molecular sensor of FIG. 4A afterfabrication.

FIG. 5 is a flowchart for a manufacturing process of the molecularsensor of FIG. 4B according to an embodiment utilizing high incidentangle oblique deposition.

FIG. 6 is a flowchart for an additional manufacturing process accordingto an embodiment.

FIG. 7A is a cross section of a molecular sensor showing the depositionof a mask line during the manufacturing process of FIG. 6.

FIG. 7B is a cross section of the molecular sensor of FIG. 7A afterdepositing a dielectric cover layer and removing the mask line of FIG.7A.

FIG. 8 is a cross section of the molecular sensor of FIG. 7Billustrating the roughening of an exposed portion of electrode sheetsaccording to an embodiment.

FIG. 9 is a top view of a molecular sensor with diverging leadconductors according to an embodiment.

FIG. 10 is a top view of the molecular sensor of FIG. 9 with a gateelectrode according to an embodiment.

FIG. 11 is a top view of a molecular sensor with channels forintroducing a fluid to pairs of electrode sheets according to anembodiment.

FIG. 12 depicts a molecular sensor manufactured by forming a stack oflayers and slicing through the stack according to an embodiment.

FIG. 13 is a flowchart for a manufacturing process of the molecularsensor of FIG. 12 according to an embodiment.

FIG. 14A is a cross section of a stack of layers during themanufacturing process of FIG. 13.

FIG. 14B illustrates the slicing of the stack of FIG. 14A to form chipsduring the manufacturing process of FIG. 13.

FIG. 14C is a cross section view showing the placement of a chip fromFIG. 14B on a substrate during the manufacturing process of FIG. 13.

FIG. 15 illustrates the placement of multiple chips on a substrateaccording to an embodiment.

FIG. 16 illustrates the placement of a dielectric cover layer on themultiple chips of FIG. 15 according to an embodiment.

FIG. 17 is a top view of a molecular sensor with diverging leadconductors according to an embodiment.

FIG. 18 is a top view of a molecular sensor with channels forintroducing a fluid to pairs of electrode sheets according to anembodiment.

DETAILED DESCRIPTION

In the following detailed description, numerous specific details are setforth to provide a full understanding of the present disclosure. It willbe apparent, however, to one of ordinary skill in the art that thevarious embodiments disclosed may be practiced without some of thesespecific details. In other instances, well-known structures andtechniques have not been shown in detail to avoid unnecessarilyobscuring the various embodiments.

The cross-section views of FIGS. 1A to 1C illustrate an examplefabrication process of a molecular sensor 100 by using a low depositionangle or by a sideways incident film deposition of thin films and thickfilms, relative to a substrate plane 103. A tri-layer thin filmstructure or device stack 111 is sequentially deposited with a firstelectrode sheet 107, an inner dielectric sheet 108, and a secondelectrode sheet 115. The tri-layer deposition is repeated with athicker, separating outer dielectric sheet 112 deposited betweenadjacent tri-layer device stacks 111 according to an embodiment.

As shown in FIGS. 1A to 1C, sensor 100 includes a supporting substrate102 with a protrusion 104 protruding from the substrate 102 at an angleto a substrate plane 103 defined by the substrate 102. The supportingsubstrate 102 can include, for example, SiO₂ or Si with a SiO₂ coating.In the example of FIG. 1, the protrusion 104 is a block that extendsfrom the substrate 102 perpendicular to the substrate plane 103. Inother implementations, the protrusion 104 may protrude from thesubstrate 102 at a different angle such as a 45 or 60 degree angle.

The protrusion 104 includes a dielectric such as SiO₂, Al₂O₃, or MgO,for example. In some implementations, the protrusion 104 can be formedby removing portions of the substrate 102 or by attaching the dielectricblock of protrusion 104 to the substrate 102. The protrusion 104 canprovide structural support for depositing dielectric and electrodelayers at an angle to the substrate plane 103.

FIG. 1A represents a thin film and thick film deposition process usingsacrificial top and side layers 119 to enable sideways deposition ofmultiple tri-layer device stacks 111. In the example of FIG. 1A, thedeposition angle can be horizontal as shown by the arrows on the rightside of FIG. 1A, or may be within plus or minus 20 degrees fromhorizontal. A first conductive electrode sheet 105 is thin filmdeposited at a sideways or low deposition angle, followed by an innerdielectric sheet 108, and then a second electrode sheet 115. Thisprocess can be repeated to form many device stacks 111, each including apairs of electrode sheets 106 with an inner dielectric sheet 108 betweenthe pair of electrode sheets 106.

A thicker dielectric sheet 112 is deposited between each tri-layerdevice stack. The relative size shown for the tri-layer device stacks111 may be somewhat exaggerated to better illustrate the features of thetri-layer device stacks 111. In this regard, the cross section width ofthe tri-layer device stacks in some embodiments may be less than 50 nm.

FIG. 1B illustrates the addition of a mechanically supportive blockmaterial 123 to facilitate polishing of the material from the top andplanarizing the device array structure along plane 117. Block material123 can include, for example, an oxide or a precursor of oxide (e.g.,hydrogen silsesquioxane (HSQ)). FIG. 1C provides a cross section view ofthe molecular sensor 100 after planarizing along plane 117.

FIG. 2A demonstrates use of detachable top and side shades 121 to enablesideways or low angle deposition of multiple tri-layer thin film devicestacks 111. A first conductive electrode sheet 105 is thin filmdeposited at a low deposition angle, followed by an inner dielectricthin film sheet 108, and then a second electrode sheet 115. This processis repeated to form multiple device stacks 111, with a thickerdielectric separator sheet 112 deposited between adjacent tri-layerstacks 111.

FIG. 2B illustrates the addition of a mechanically supportive blockmaterial 123 such as oxide or precursor of oxide (e.g., HSQ) to thestructure of FIG. 2A after removal of the shades 121. The supportiveblock material 123 can facilitate polishing of the material from the topand planarizing the device array structure along plane 117. FIG. 2Cprovides a cross section view of the molecular sensor 100 afterplanarizing along plane 117.

The molecular sensors 100 as shown in the examples of FIGS. 1C and 2Cutilize a unique geometry of electrodes in a vertically alignedtri-layer sheet configuration. The sheet geometry of the electricallyconductive electrodes ordinarily allows for a low electrical resistanceof the sensor electrodes to enable a desirably high signal-to-noiseratio, with accurate dimensional control, and ease of scale-upfabrication at a relatively low cost. This configuration can facilitatethe packing of high-density device arrays using a low device surfacearea real estate, allowing the manufacture of a multiple deviceassembly. The deposition of conductor layer, dielectric layer, andsecond conductor layer can be repeated many times. In this regard, thissequence of deposition may be repeated 2 to 10,000 times to produce anarray of 2 to 10,000 parallel devices.

The tri-layer device stack 111 can include highly electricallyconductive metallic electrode sheets in a vertical or near-verticalconfiguration. Other implementations can include a tilted angleorientation of up to about a 60 degree tilting of the electrode sheetsfrom a vertical alignment, but preferably with less than 20 degrees oftilting. Each pair of electrode sheets 106 is separated in the devicestack 111 by a dielectric sheet layer material 108 that can be selectedfrom oxides (e.g., SiO₂, Al₂O₃, MgO, CaO, refractory oxide, rare earthoxide or a mixture of oxides), nitrides (e.g., AlN, Si₃N₄, refractorynitride, rare earth nitride or a mixture of nitrides), fluoride,oxyfluoride, or oxynitride.

The material for the electrodes 107 and 115 is desirably selected fromhigh-conductivity metals or alloys such as Au, Pt, Pd, Ag, Os, Ir, Rh,Ru and their alloys. The dimension of the exposed electrode sheet on thedevice top surface can have a thickness or width, for example, of 2 to100 nm. Depending on design considerations such as the molecule to beanalyzed, the electrode sheets 107 and 115 in FIGS. 1A and 2A can bedeposited with a thickness of 1 to 40 nm or preferably 5 to 15 nm, withthe height of a vertical or near-vertical electrode sheet beingdesirably at least 100 μm tall, preferably at least 1,000 μm tall, andeven more preferably at least 10,000 μm tall. Accordingly, the desiredaspect ratio of the electrode sheet, in terms of height to thickness, isat least 10,000, and preferably at least 100,000.

In some implementations, a thin adhesion enhancing layer may bedeposited at the interface between the electrode sheets and the innerdielectric sheet to improve the adhesion at the interface. In oneexample, a 1 to 5 nm thick film material is deposited at the interfaceusing a material such as Ti, Cr, Al, Zr. Mo, Nb, Ta, or Hf

The dimension of the exposed dielectric sheet 108 between the twoelectrode sheets on the device top surface is desirably in the range of1 to 40 nm thick or wide, and preferably 5 to 15 nm thick. In someimplementations, the thickness of the inner dielectric sheets 108 can beat most 10 nm. The height of a vertical or near-vertical dielectricsheet 108 is desirably at least 100 μm tall, preferably at least 1,000μm tall, and even more preferably at least 10,000 μm tall. Accordingly,the desired aspect ratio of the inner dielectric layer sheet, in termsof height to thickness, is at least 10,000, and preferably at least100,000.

The dimension of the outer dielectric layer 112 that separatesneighboring tri-layer device stacks 111, has a desirable thickness (orwidth) range of at least 500 to 20,000 nm that is at least one order ofmagnitude greater than the thickness of the inner dielectric sheet. Apreferred thickness for the outer dielectric layer 112 can be, forexample, in the range of 500 to 5,000 nm. The separation betweenadjacent tri-layer device stacks 111 reduces electrical, inductive,capacitive, or other interferences.

As discussed in more detail below with reference to FIG. 3, themolecular sensor 100 can be formed using a low incident angle obliquedeposition of layers, such as at a deposition angle of 0 to less thanplus or minus 20 degrees from the substrate plane 103. In the exampleprocess of FIG. 3, a low incident angle oblique deposition is used withone or more sacrificial layers (e.g., sacrificial layers 119 in FIG. 1A)and/or detachable shades (e.g., detachable shades 121 in FIG. 2A) tohelp prevent deposition of the electrode and dielectric layers oncertain surfaces. The sacrificial layers and detachable shades are laterremoved after the electrode and dielectric sheets have been formed at anangle to the substrate plane 103.

In the example of FIG. 1A, a series of film depositions are performed ata deposition angle of 0 to less than plus or minus 20 degrees from thesubstrate plane 103. The sacrificial layer 119 acts as a dummy,disposable material on a surface of the protrusion 104 opposite thesubstrate 102. In some implementations, the sacrificial layer 119 caninclude a slight extension off the edge of the protrusion 104 to helpprevent deposition above the top surface of the protrusion 104.

FIG. 5 discussed below provides an alternative example process thatincludes performing the multilayer deposition at a higher obliqueincident angle and followed by planarization. The higher obliqueincident angle for multilayer deposition can be performed, for example,at any angle in the range of 20 to 70 degrees from the substrate plane103, with a preferred deposition angle between 30 degrees and 60degrees. With an oblique angle deposition without a sacrificial layer asin the process of FIG. 5, the surface of the protrusion 104 opposite thesubstrate 102 is also covered with multilayer thin films, as illustratedin FIG. 4A. A planarization polishing process, after the attachment of amechanically supportive block material, removes the film deposition onthe surface of the protrusion 104 opposite the substrate 102 so as toachieve a structure as in FIG. 4B.

With reference to the flowchart of FIG. 3, in block 302, a substratesuch as the substrate 102 is provided defining a substrate plane. Thesubstrate plane can be defined by being parallel with a surface of thesubstrate such as a top or bottom surface for supporting dielectric andelectrode layers.

In block 304, a protrusion (e.g., protrusion 104) is attached to thesubstrate or the protrusion is formed by removing one or more portionsof the substrate. As noted above, the protrusion extends or protrudesfrom the substrate plane at an angle, such as 90 degrees. In oneexample, the protrusion can be a cut-out step of an initially thickersupporting substrate. In another example, a dielectric block or othershape may be attached to a supporting substrate to form the protrusionat an angle to the substrate plane.

With reference to FIG. 3, in block 305, one or more sacrificial layersand/or detachable shades are placed on a side to be deposited (e.g.,detachable shades 121 in FIG. 2A) and/or a surface of the protrusionopposite the substrate (e.g., the top sacrificial layer 119 in FIG. 1A).As noted above, the sacrificial layer may extend beyond the edge of theprotrusion 104. The sacrificial layer can include, for example, aphysically removable plate, or a dissolvable polymer layer, such asacetone-dissolvable polymethyl methacrylate (PMMA) that is often usedfor lift-off processing in semiconductor fabrication. The detachableshade can include, for example, a detachable metallic, ceramic, orpolymer material.

In block 306, a first electrode layer is deposited on the substrate. Atleast a portion of the first electrode layer is deposited in anorientation along a side of the protrusion to form a first electrodesheet (e.g., first electrode sheet 107 in FIG. 1A or in FIG. 2A) at theangle to the substrate plane. In other implementations, an initialdielectric layer may be deposited before the first electrode layer isdeposited in block 306.

In the example process of FIG. 3, an inner dielectric layer is depositedin block 308 on the first electrode layer deposited in block 306. Asshown in the examples of FIGS. 1A and 2A, at least a portion of theinner dielectric layer is deposited in the orientation along theprotrusion 104 to form the inner dielectric sheet 108 at the angle tothe substrate plane 103. As with the first electrode layer deposited inblock 306, oblique incident deposition can be used to deposit the innerdielectric layer at the angle to the substrate plane. Standardcomplementary metal-oxide semiconductor (CMOS) processes such as obliqueincident deposition can ordinarily allow for the inner dielectric layerto be deposited with an accurate and repeatable thickness.

In some implementations, a thin adhesion enhancing layer may bedeposited on the first electrode layer before and/or after depositingthe inner dielectric layer to improve adhesion of the layers. In oneexample, a 1 to 5 nm thick film material is deposited at the interfaceusing a material such as Ti, Cr, Al, Zr. Mo, Nb, Ta, or Hf.

In block 310, a second electrode layer is deposited on the innerdielectric layer to form a second electrode sheet (e.g., secondelectrode sheet 115 in FIGS. 1A and 2A) at the angle to the substrateplane, using, for example, oblique incident deposition. The firstelectrode sheet and the second electrode sheet form a pair of electrodesheets with the inner dielectric sheet between the first electrode sheetand the second electrode sheet.

In block 312, an outer dielectric layer is deposited on the secondelectrode layer to form an outer dielectric sheet at an angle to thesubstrate plane. With reference to the examples in FIGS. 1A and 2A, theouter dielectric layer is deposited on the second electrode layer toform the outer dielectric sheet 112 at an angle to the substrate plane103. In some implementations, the outer dielectric layer may have adifferent thickness if it is a final outer dielectric layer to, forexample, facilitate packaging of the sensor in a larger array of sensorsor to provide a greater exterior insulation.

In block 314, it is determined whether a final number of pairs ofelectrode sheets has been reached. In some implementations, the finalnumber of pairs of electrode sheets may be as few as two pairs ofelectrode sheets. In this regard, the sub-process of blocks 306 to 312is repeated at least once to provide for at least two pairs of electrodesheets. In some implementations, the final number of pairs of electrodesheets may be as large as several thousand pairs of electrode sheets forexample. The final number of pairs of electrode sheets may depend on thedesign considerations for the sensor being manufactured, such as adesired testing speed, a type of molecule to be analyzed, or a desiredfootprint for the sensor.

If the final number of pairs of electrode sheets has not been reached inblock 314, the process returns to block 306 to deposit another firstelectrode layer in an orientation along a side of the protrusion to formanother first electrode sheet at an angle to the substrate plane.

On the other hand, if the final number of pairs of electrode sheets hasbeen reached in block 314, the process proceeds to block 315 to removesacrificial layers or detachable shades added in block 305 above. Thesacrificial layer can, for example, be physically removed or removed bydissolving the sacrificial layer and the detachable shade can bephysically removed. In one example, the sacrificial layer is dissolvedusing a liquid, as in lift-off processing.

At least one mechanically supportive block material is also added inblock 315 with a gap-filling curable polymer. A mechanically supportiveblock material may be attached adjacent the deposited multilayer stack(e.g., block 123 added to the right of the deposited layers shown inFIGS. 1B and 2B). In some implementations, this is accomplished byattaching a block of ceramic material or polymer material, or bydepositing a polymer material and curing. The gap between the addedsupporting block and the previously deposited multilayers can be filledwith a UV-curable, electron beam curable, or thermally curable polymersuch as PMMA or hydrogen silsesquioxane (HSQ) resist. The HSQ resistlayer deposited can be hardened by additional thermal curing to be closeto a SiO₂ type harder material. The mechanically supportive blockmaterial can be added for subsequent planarization, as in optional block316, or to provide support for handling, such as during a subsequentpackaging process of the molecular sensor 100.

Optional block 316 includes planarizing the pairs of electrode sheets,the inner dielectric sheets, and the one or more outer dielectric sheetsformed by repeating the sub-process of blocks 306 to 312. Theplanarizing can include, for example, CMP polishing, focused ion beam(FIB) etching, or PMMA or HSQ filling and etching back by reactive ionetch (RIE). After the repeated deposition of thin film and thick filmelectrodes and dielectric layers, the mechanically supportive blockmaterial added and cured in block 315, such as a SiO₂ material orprecursor of SiO₂ (e.g., HSQ), can provide support during planarization.

With reference to FIGS. 1B or 2B, planarization can take place along theplanarization line 117 below a top surface of the protrusion 104. Inother implementations, planarization can take place along the topsurface of the protrusion 104 so that an exposed top surface of theelectrode sheets and dielectric sheets is substantially planar with atop surface of the protrusion 104 or parallel to the substrate plane103.

In some implementations, block 316 in FIG. 3 may be omitted such aswhere a sacrificial layer extended far enough over an edge of theprotrusion to prevent unwanted deposition on the top of the protrusion.In such an example, removal of the sacrificial layer in block 315 mayresult in the exposed top surfaces of the pairs of electrode sheetswithout the need for planaraization.

FIG. 4A is a cross section view showing fabrication of a molecularsensor 100 by sequentially depositing tri-layer thin film device stacksusing a high deposition angle according to an embodiment. FIG. 4Bprovides a cross section view of the molecular sensor 100 of FIG. 4Aafter fabrication.

The dielectric layers in FIG. 4A include the inner dielectric layers 109and the outer dielectric layers 115. As with the protrusion 104, theinner dielectric layers 109 and the outer dielectric layers 115 caninclude, for example, a dielectric such as SiO₂, Al₂O₃, or MgO. As shownin FIG. 4A, a first portion of the inner dielectric layers 109 and theouter dielectric layers 115 are deposited in an orientation along thesubstrate plane 103 (i.e., horizontally in the example of FIG. 4A). Asecond portion of the inner dielectric layers 109 and the outerdielectric layers 115 are deposited in an orientation along theprotrusion 104 (e.g., vertically onto the right side of the protrusion104 in the example of FIG. 4A) to form the inner dielectric sheets 108and the outer dielectric sheets 112, respectively. The inner dielectricsheets 108 and the outer dielectric sheets 112 are formed at an angle tothe substrate plane 103.

The electrode layers in FIG. 4A include the first electrode layers 105and the second electrode layers 113. The electrode layers can include,for example, a conductive metal such as Au, Pt, Pd, Ag, or Rh.

As shown in FIG. 4A, a first portion of the first electrode layers 105and the second electrode layers 113 are deposited in an orientationalong the substrate plane 103 (i.e., horizontally in the example of FIG.1). A second portion of the first electrode layers 105 and the secondelectrode layers 113 are deposited along the protrusion 104 (e.g.,vertically onto the right side of the protrusion 104 in the example ofFIG. 1) to form the first electrode sheets 107 and the second electrodesheets 115, respectively. The first electrode sheets 107 and the secondelectrode sheets 115 are formed at an angle to the substrate plane 103.

Depositing the electrode layers and the dielectric layers at an angle tothe substrate plane 103 can allow for exposing multiple pairs ofelectrode sheets 106. This can ordinarily allow for scalability infabricating a large number of electrode pairs 106 by depositing manyelectrode and dielectric layers.

For example, a sequence of film deposition can include depositing afirst conductor layer 105, followed by an inner dielectric layer 109,then followed by a deposition of a second conductor layer 113 to bepaired with the first conductor layer 105, with the inner dielectriclayer 109 being sandwiched by the first conductor layer 105 and secondconductor layer 113. An outer dielectric layer 118 is then depositedwith a sufficient thickness to separate the earlier-deposited conductorpair from a subsequent conductor pair. The deposition of conductorlayer, dielectric layer, and second conductor layer can be repeated manytimes.

In addition to scalability, the thickness of the inner dielectric sheets108 can be accurately controlled using standard CMOS type thin filmdeposition fabrication processes as with the examples of FIGS. 1C and 2Cdiscussed above. This can ordinarily allow for a fixed and accuratelycontrolled spacing between the two electrode sheets to facilitate areliable and reproducible attachment of particular molecules such ascertain proteins, DNAs, nucleotides, lipids, antibodies, hormones,carbohydrates, metabolites, pharmaceuticals, vitamins,neurotransmitters, enzymes, or another molecule to be analyzed. The useof standard CMOS processes to produce multi-electrode molecule sensingdevices also reduces the costs typically associated with manufacturing amolecule sensor.

Each electrode sheet in FIG. 4B can have a thickness, for example, of 2to 100 nm. Depending on design considerations such as the molecule to beanalyzed, the electrode sheets and layers 107/105 and 115/113 can bedeposited with a thickness of 1 to 40 nm or 5 to 15 nm. In suchimplementations, the inner dielectric sheets and layers 108/109 can bedeposited with a similar thickness of 1 to 40 nm or 2 to 15 nm, but theouter dielectric sheets and layers 112/118 are deposited with athickness between 50 to 2,000 nm that is at least one order of magnitudegreater than the thickness of the inner dielectric sheets and layers108/109.

The exposed first electrode sheets 107 and the exposed second electrodesheets 115 form pairs of electrode sheets 106 with a portion of theinner dielectric sheet 108 partially removed to form a groove or a gap110. The free space of the gap 110 between the two electrode sheets canallow the molecules 10 to be more conveniently attached as shown in FIG.4B. The molecules 10 can include, for example, a protein, DNA,nucleotide, lipid, antibody, hormone, carbohydrate, metabolite,pharmaceutical, vitamin, neurotransmitter, enzyme, or another type ofmolecule to be analyzed or identified.

One electrode sheet in the pair of electrode sheets 106 can serve as asource electrode and the other electrode sheet can serve as a drainelectrode. In operation, a molecule 10 is attached to each electrodesheet in the pair of electrode sheets as shown in FIG. 4B to form amolecular bridge between the electrode sheets. The molecule 10 caninclude, for example, a protein, DNA, antibody, nucleotide, lipid,hormone, carbohydrate, metabolite, pharmaceutical, vitamin,neurotransmitter, enzyme, or another type of molecule to be identifiedor analyzed. The molecule 10 can then be detected or analyzed bymeasuring an electronic signal in the molecular sensor. In someimplementations, a current is passed through the molecule 10 by forminga circuit including the first electrode sheet 107, the second electrodesheet 115, and the molecule 10. Based on the measured current, themolecule 10 can be identified or analyzed. Such an implementation canallow the molecular sensor 100 to be used for genome sequencing.

In some implementations, sensor 100 can include up to one thousand pairsof electrode sheets 106. Sensor 100 can also provide for scalability bycombining multiple sensors such as sensor 100 together to obtain an evengreater number of pairs of electrode sheets to simultaneously test moremolecules. This scalability can ordinarily reduce the time for analyzinga large number of molecules at the same time.

As shown in FIG. 4B, each pair of electrode sheets 106 is separated byan outer dielectric sheet 112. An inner dielectric sheet 108 separatesthe first electrode sheet 107 and the second electrode sheet 115 in apair of electrode sheets 106. In some implementations, the innerdielectric sheets 108 can all have approximately a first thickness(e.g., within 5%), while all the outer dielectric sheets 112 can haveapproximately a second thickness (e.g., within 5%) that is at least oneorder of magnitude greater than the first thickness. The thicker outerdielectric sheet 112 provides separation between adjacent pairs ofelectrode sheets 106 to reduce electrical or capacitance interference.

For example, a desired thickness of the outer dielectric sheets 112 canbe at least 1 μm or at least 10 μm, while a desired thickness for theinner dielectric sheets 112 can be at most 50 nm or at most 20 nm. Insome implementations, the thickness of the inner dielectric sheets 112can be at most 10 nm. Having an accurately controlled inner dielectriclayer thickness can ordinarily improve the reliable and reproducibleattachment of certain molecules to the pairs of electrode sheets 106,which results in more accurate readings from the sensor 100 since it isless likely that other types of molecules inadvertently attach to theelectrode sheets.

A groove or gap 110 in the inner dielectric sheet 108 can facilitate theattachment of a molecule 10 for analysis during operation. In someimplementations, a partial air gap can be introduced by localizedetching or by deposition with local masking to form a groove 110 in theinner dielectric sheet 108. For example, a space 5 to 15 nm deep fromthe exposed edge of the inner dielectric sheet 108 can be etched toproduce a free spacing to facilitate the movement and attachment ofcertain biomolecules.

FIG. 5 is a flowchart for a manufacturing process of the molecularsensor of FIG. 4B according to an embodiment utilizing a relatively highincident angle oblique deposition. In the example process of FIG. 5, ahigher incident angle oblique deposition is used than in the exampleprocess of FIG. 3 so that the electrode and dielectric layers are alsodeposited on the surface of the protrusion 104 opposite the substrate102 (i.e., the top surface of the protrusion 104 in FIG. 4A). The layersare later planarized to expose the electrode sheets and dielectricsheets that have been formed at an angle to the substrate plane 103.

In comparison to the process of FIG. 3, the process of FIG. 5 generallydoes not include the placement of sacrificial layers or detachableshades as in block 305 of FIG. 3, or the removal of such sacrificiallayers or detachable shades as in block 315 of FIG. 3. The higherdeposition angle can usually prevent the unwanted deposition of layerswithout using sacrificial layers or detachable shades.

In block 502, a substrate such as the substrate 102 is provided defininga substrate plane. The substrate plane can be defined by being parallelwith a surface of the substrate such as a top or bottom surface forsupporting dielectric and electrode layers.

In block 504, a protrusion (e.g., protrusion 104) is attached to thesubstrate or the protrusion is formed by removing one or more portionsof the substrate. As noted above, the protrusion extends or protrudesfrom the substrate plane at an angle, such as 90 degrees. In oneexample, the protrusion can be a cut-out step of an initially thickersupporting substrate. In another example, a dielectric block or othershape may be attached to a supporting substrate to form the protrusionat an angle to the substrate plane.

In block 506, a first electrode layer is deposited on the substrateusing a relatively high angle of deposition, such as between 20 and 70degrees from the substrate plane. At least a portion of the firstelectrode layer is deposited in an orientation along a side of theprotrusion to form a first electrode sheet (e.g., first electrode sheet107 in FIG. 4A) at the angle to the substrate plane. In otherimplementations, an initial dielectric layer may be deposited before thefirst electrode layer is deposited in block 506.

In the example process of FIG. 5, an inner dielectric layer is depositedin block 508 on the first electrode layer deposited in block 506. Asshown in the example of FIG. 4A, at least a portion of the innerdielectric layer is deposited in the orientation along the protrusion104 to form the inner dielectric sheet 108 at the angle to the substrateplane 103. As with the first electrode layer deposited in block 506,oblique incident deposition can be used to deposit the inner dielectriclayer at the angle to the substrate plane. Standard CMOS processes suchas oblique incident deposition can ordinarily allow for the innerdielectric layer to be deposited with an accurate and repeatablethickness.

In some implementations, a thin adhesion enhancing layer may bedeposited on the first electrode layer before and/or after depositingthe inner dielectric layer to improve adhesion of the layers. In oneexample, a 1 to 5 nm thick film material is deposited at the interfaceusing a material such as Ti, Cr, Al, Zr. Mo, Nb, Ta, or Hf.

In block 510, a second electrode layer is deposited on the innerdielectric layer to form a second electrode sheet (e.g., secondelectrode sheet 115 in FIG. 4A) at the angle to the substrate plane,using, for example, oblique incident deposition. The first electrodesheet and the second electrode sheet form a pair of electrode sheetswith the inner dielectric sheet between the first electrode sheet andthe second electrode sheet.

In block 512, an outer dielectric layer is deposited on the secondelectrode layer to form an outer dielectric sheet at an angle to thesubstrate plane. With reference to the example in FIG. 4B, the outerdielectric layer is deposited on the second electrode layer to form theouter dielectric sheet 112 at an angle to the substrate plane 103. Insome implementations, the outer dielectric layer may have a differentthickness if it is a final outer dielectric layer to, for example,facilitate packaging of the sensor in a larger array of sensors or toprovide a greater exterior insulation.

In block 514, it is determined whether a final number of pairs ofelectrode sheets has been reached. In some implementations, the finalnumber of pairs of electrode sheets may be as few as two pairs ofelectrode sheets. In this regard, the sub-process of blocks 506 to 512is repeated at least once to provide for at least two pairs of electrodesheets. In some implementations, the final number of pairs of electrodesheets may be as large as several thousand pairs of electrode sheets forexample. The final number of pairs of electrode sheets may depend on thedesign considerations for the sensor being manufactured, such as adesired testing speed, a type of molecule to be analyzed, or a desiredfootprint for the sensor.

If the final number of pairs of electrode sheets has not been reached inblock 514, the process returns to block 506 to deposit another firstelectrode layer in an orientation along a side of the protrusion to formanother first electrode sheet at an angle to the substrate plane.

On the other hand, if the final number of pairs of electrode sheets hasbeen reached in block 514, the process proceeds to block 515 to add atleast one mechanically supportive block material with a gap-fillingcurable polymer. A mechanically supportive block material may beattached adjacent the deposited multilayer stack (e.g., block 123 addedto the right of the deposited layers shown in FIG. 4A). In someimplementations, this is accomplished by attaching a block of ceramicmaterial or polymer material, or by depositing a polymer material andcuring. The gap between the added supporting block and the previouslydeposited multilayers can be filled with a UV-curable, electron beamcurable, or thermally curable polymer such as PMMA or HSQ resist. TheHSQ resist layer deposited can be hardened by additional thermal curingto be close to a SiO₂ type harder material. The mechanically supportiveblock material is added for subsequent planarization, as in block 516,or to provide support for handling, such as during a subsequentpackaging process of the molecular sensor 100.

Block 516 includes planarizing the pairs of electrode sheets, the innerdielectric sheets, and the one or more outer dielectric sheets formed byrepeating the sub-process of blocks 506 to 512. The planarizing caninclude, for example, CMP polishing, FIB etching, or PMMA or HSQ fillingand etching back by RIE. After the repeated deposition of thin film andthick film electrodes and dielectric layers, the mechanically supportiveblock material added and cured in block 515, such as a SiO₂ material orprecursor of SiO₂ (e.g., HSQ), can provide support during planarization.With reference to FIG. 4A, planarization can take place along theplanarization line 117, which is along the top surface of the protrusion104 so that an exposed top surface of the electrode sheets anddielectric sheets is substantially planar with a top surface of theprotrusion 104 or parallel to the substrate plane 103. In otherimplementations, the planarization can take place below the top surfaceof the protrusion 104 to expose the pairs of electrode sheets.

FIG. 6 is a flowchart for a manufacturing process that can follow themanufacturing process of either FIG. 3 or FIG. 5 according to anembodiment. In block 602, a groove is formed on an exposed end portionof each inner dielectric sheet. As noted above, the groove or gap can beformed by etching the inner dielectric sheet using an etching processsuch as RIE, sputter etch, or a chemical etch like HF etch. In oneimplementation, an electrical, capacitance, or optical measurement suchas a voltage, electrical resistance, or optical penetration orinterference can be measured between the first electrode sheet and thesecond electrode sheet to form the groove to a particular depth. In suchan implementation, etching can be performed until the measurementreaches a threshold value corresponding to the desired depth of thegroove. Further removal of the inner dielectric sheet is then stoppedbased on the electrical measurement reaching the threshold value.

In block 604, a dielectric cover layer is optionally deposited to definea gap exposing a portion of the plurality of pairs of electrode sheets.In some implementations, a mask line is deposited across an end portionof the pairs of electrode sheets and the dielectric cover layer isdeposited on at least one side of the mask line to cover a remainingexposed portion of the pairs of electrode sheets not covered by the maskline. The mask line is then removed so that the dielectric cover layerdefines a gap exposing the end portion of the pairs of electrode sheets.In other embodiments, block 604 may be omitted such that the depositionof the mask line and the dielectric cover layer is not performed.

By limiting the exposed area of the pairs of electrode sheets, it isordinarily possible to improve the accuracy of the sensor because thegap can prevent more than one molecule from attaching to the electrodesheets in each pair of electrode sheets. When more than one moleculeattaches, the readings for the pair of electrode sheets are affected. Inthe case where a current is measured between the electrode sheets viathe molecule, the attachment of multiple molecules between the electrodesheets can lower the current measured across the electrode plates andlead to an inaccurate measurement. In some implementations, the gapdefined by the dielectric cover layer is between approximately 2 to 40nanometers depending on the type of molecule to be attached. In someimplementations, the width of the gap can be between 5 and 15 nm wide.

FIG. 7A is a cross section showing the deposition of a mask line 114across pairs of electrode sheets 106. The mask line 114 can be depositedusing, for example, an HSQ resist. As shown in FIG. 7B, a dielectriccover layer 116 is deposited on both sides of the mask line 114. Thedielectric cover layer 116 can include, for example, a SiO₂ layer. Afterremoval of the mask line 114, only the end portion of the electrodesheet pairs in the gap 118 are exposed for attaching a single molecule10 to each exposed pair of electrode sheets. In other implementations,the gap 118 may be formed by using a patterning process such as e-beamlithography or nano-imprinting, and etching an unmasked region to formthe gap 118. In some examples, the gap 118 can have a width between 2 to40 nm or 5 to 15 nm to facilitate the attachment of a single molecule ateach pair of electrode sheets 106.

Returning to the manufacturing process of FIG. 6, an exposed edge ofeach electrode sheet can be roughened in block 606 to improve theattachment of a molecule to the edge of the electrode sheet. FIG. 8illustrates the roughening of an exposed portion of the first electrodesheets 107 and the second electrode sheets 115 according to anembodiment. The exposed portions of the electrode sheets in gap 118 maybe roughened by, for example, dealloying of a base alloy (e.g.,dealloying an Au—Ag alloy), mechanical sand blasting, ion bombardment,electron bombardment, ion implantation, chemical etching, orelectrochemical etching. The surface roughening may include a featuresize of 0.5 to 20 nm. In some examples, the surface roughening featuresize can be between 1 to 10 nm, or between 1 to 5 nm.

The roughening of the exposed edges of the electrode sheets ordinarilyprovides for easier and more secure molecular attachment due to thehigher surface area of the roughened surface. Other processes may beperformed on the exposed edges of the electrode sheets to improveattachment of the analyte molecule. Examples of such processes caninclude the nano-tip or nano-pillar conductive islands discussed in U.S.Provisional Application No. 62/288,364, entitled “Massively Parallel DNASequencing Apparatus Comprising Strongly Adhered Conductor Nanotips andNanoparticles, Method of Fabrication, and Applications Thereof”, andfiled by the present Applicant on Jan. 28, 2016, the entire contents ofwhich are hereby incorporated by reference. Other examples of improvingthe attachment of the analyte molecule, such as using conductive islandswith reduced contact resistance, can be found in U.S. ProvisionalApplication No. 62/293,239, entitled “Electronic, Label-Free DNA andGenome Sequencing Apparatus, Method of Fabrication, and ApplicationsThereof”, and filed by the present Applicant on Feb. 9, 2016, the entirecontents of which are hereby incorporated by reference.

Returning to the process of FIG. 6, a plurality of lead conductors areconnected to the plurality of electrode sheets in block 608, with eachlead conductor connected to a respective electrode sheet. As shown inthe example of FIG. 9, the lead conductors 120 diverge in width as thelead conductor extends away from an edge of the electrode sheet towardthe contact 122. The lead conductors can be made of a conductivematerial such as gold for carrying a test signal from the electrodesheets. In some implementations, the thickness of the electrode sheetscan be as small as only 10 nm. The lead conductors may then fan out froma width of approximately 10 nm to a scale of micrometers to allow forsoldering at the contacts 122. The contacts 122 can include a contactpad array for circuit packaging, solder bonding, or wire bonding.

As shown in FIG. 9, a dielectric cover layer 124 may also be applied sothat only a portion of the pairs of electrode sheets 106 are exposed.The dielectric cover layer may also cover a portion of the leadconductors 120. In some implementations, the dielectric cover layer 124can have a thickness of 1 to 20 nm or 1 to 10 nm of a dielectricmaterial such as SiO₂, Al₂O₃, MgO, PMMA, or polydimethylsiloxane (PDMS).Similar to the dielectric cover layer discussed above for block 604, thedielectric cover layer 124 in FIG. 9 can improve the accuracy ofreadings by facilitating the attachment of only one molecule per pair ofelectrode sheets 106. In this regard, only one molecule 10 is shownattached to each pair of electrode sheets 106.

In some implementations, multiple molecular sensors such as the blockshown in FIG. 9 may be joined together for scalability. For example, 1to 1,000 blocks may be joined together, with each block including 100 to5,000 pairs of electrode sheets 106. The joined blocks may then beplanarized to the same height using, for example, CMP polishing, FIBetching, PMMA or HSQ filling and etching back by RIE. This can alsoallow for the placement of electrical circuits or components on thejoined blocks.

In block 610 of FIG. 6, a gate electrode is optionally depositedparallel to the substrate plane and perpendicular to an electrode planedefined by an electrode sheet. The gate electrode can include, forexample, a Si or metallic electrode placed on a side of the substrateopposite the electrode sheets or near a front portion of the electrodesheets on the same side of the substrate as the electrode sheets. FIG.10 discussed below provides examples showing the placement of electrodegates in these locations.

As shown in FIG. 10, the electrode gate 126 is located near the frontportion of the electrode sheets and extends along a length of theelectrode sheets in a direction perpendicular to the electrode sheetplane 125 defined by one of the electrode sheets. The electrode gate 127is located on the backside of the substrate 102 extending across thesubstrate 102 in a direction perpendicular to the electrode sheet plane125.

The addition of an electrode gate can ordinarily improve the accuracy ofreadings from the pairs of electrode sheets by imposing an electricfield to regulate the charge carriers between the first electrode sheetand the second electrode sheet, which serve as source and drainelectrodes. An electrode gate can be especially helpful inimplementations where the electrode sheets include a semiconductor. Onthe other hand, some implementations may not include an electrode gatesuch that block 608 may be omitted from the process of FIG. 6.

In some implementations, the arrangement of FIG. 10 can include one ormore dielectric cover layers similar to the dielectric cover layer 124in FIG. 9 discussed above. The dielectric cover layer or layers can bedeposited at an angle to or perpendicular to the electrode sheets on thesurface of the planarized structure to expose only a narrow gap portionof the electrode sheets for molecular sensing.

In block 612 of FIG. 6, a plurality of channels is optionally formedwith each channel arranged to introduce a fluid to the exposed portionsof the electrode sheets. Each channel includes at least two pairs ofelectrode sheets. As shown in the example of FIG. 11, each channel canbe formed by adding a wall 128 between a group of pairs of electrodesheets. A fluid such as a gas or liquid containing the molecules to betested can then be introduced into the channel so that multiple pairs ofelectrodes can be used to test the molecules in the fluid. In theexample of FIG. 11, each channel is loaded with a fluid containing adifferent DNA nucleobase for detection via the pairs of electrode sheets106 in the channel.

The arrangement shown in FIG. 11 can ordinarily allow for errorcorrection or compensation by loading the same fluid to be tested (e.g.,a fluid with molecules 10, 12, 14, or 16 in FIG. 11) across multiplepairs of electrode sheets 106 and using the different measurements forthe different pairs of electrode sheets to average out any error and/oreliminate a measurement that deviates by more than a threshold. Althoughthree pairs of electrode sheets are shown per channel in the example ofFIG. 11, a different number of pairs can be used in differentimplementations, such as ten or twenty pairs of electrode sheets perchannel.

In some implementations, the arrangement shown in FIG. 11 can includeone or more dielectric cover layers similar to the dielectric coverlayer 124 in FIG. 9 discussed above. The dielectric cover layer orlayers can be deposited at an angle to or perpendicular to the electrodesheets on the surface of the planarized structure to expose only anarrow gap portion of the electrode sheets for molecular sensing.

FIG. 12 provides a side view of a molecular sensor 200 according to anembodiment where the molecular sensor is manufactured by forming a stackof electrode and dielectric layers and slicing through the stack. Asshown in FIG. 12, sensor 200 includes a supporting substrate 202 thatcan include, for example, SiO₂ or Si with an SiO₂ coating. In theexample of FIG. 12, the pairs of electrode sheets 206, inner dielectricsheets 208, and outer dielectric sheets 212 are at a perpendicular angleto the substrate 202 so that the electrode sheets are in a vertical ornear-vertical configuration. Other implementations can include a tiltedangle orientation of up to about a 60 degree tilting of the electrodesheets from a vertical alignment, but preferably with less than 20degrees of tilting. In such implementations, the sheets may extend fromthe substrate 202 at an angle, such as a 45 or 60 degree angle.

The inner dielectric sheets 108 and the outer dielectric sheets 212 caninclude, for example, a dielectric such as SiO₂, Al₂O₃, or MgO. Theelectrode sheets 207 and 215 can include, for example, a conductivemetal such as Au, Pt, Pd, Ag, or Rh.

As discussed in more detail below with reference to FIG. 13, themolecular sensor 200 is formed by slicing a stack of dielectric andelectrode layers into a plurality of chips, and attaching the pluralityof chips to a substrate such as substrate 202 so that a desirablyaligned structure of electrode pairs and dielectric spacers is obtained.This can ordinarily allow for fabricating a large number of electrodesheet pairs 206 by attaching multiple chips and/or using multiple layersin forming the stack.

The alignment of layers at an angle to the substrate 202, as opposed toparallel to the substrate 202, improves control of the degree of etchingof the inner dielectric sheets 208. This can allow for a more accurateand reproducible cavity structure or grooves 210 to provide for easierattachment of a single molecule for analysis when DNA, a nucleotide, orother analyte is attached. In addition, and as with the molecular sensor100 discussed above, the thickness of the inner dielectric layers 208can be accurately controlled using standard CMOS fabrication processesto facilitate the attachment of particular molecules such as proteins,DNAs, nucleotides or another molecule to be analyzed. The use ofstandard CMOS processes to produce multi-electrode molecule sensingdevices also reduces the costs typically associated with manufacturing amolecule sensor.

The exposed first electrode sheets 207 and the exposed second electrodesheets 215 form pairs of electrode sheets 206 for attaching molecules10. One electrode sheet in the pair of electrode sheets 206 can serve asa source electrode and the other electrode sheet can serve as a drainelectrode. In operation, a molecule 10 is attached to each electrodesheet in the pair of electrode sheets as shown in FIG. 12 to form amolecular bridge. The molecule 10 can include, for example, a protein,DNA, antibody, nucleotide, lipid, hormone, carbohydrate, metabolite,pharmaceutical, vitamin, neurotransmitter, enzyme, or another type ofmolecule to be identified or analyzed. The molecule 10 can then bedetected or analyzed by measuring an electronic signal in the molecularsensor. In some implementations, a current can be passed through themolecule 10 by forming a circuit including the first electrode sheet207, the second electrode sheet 215, and the molecule 10. Based on themeasured current, the molecule 10 can be identified or analyzed. Such animplementation can allow the molecular sensor 100 to be used for genomesequencing.

In some implementations, sensor 200 can include up to one thousand pairsof electrode sheets 206. Sensor 200 can also provide for scalability bycombining multiple sensors such as sensor 200 together to obtain an evengreater number of pairs of electrodes to simultaneously test moremolecules. This scalability can ordinarily reduce the time for analyzinga large number of molecules at the same time.

As shown in FIG. 12, each pair of electrode sheets 206 is separated byan outer dielectric sheet 212. An inner dielectric sheet 208 separatesthe first electrode sheet 207 and the second electrode sheet 215 in apair of electrode sheets 206. In some implementations, the innerdielectric sheets 208 can all have approximately a first thickness(e.g., within 5%), while all the outer dielectric sheets 212 can haveapproximately a second thickness (e.g., within 5%) that is at least oneorder of magnitude greater than the first thickness. The thicker outerdielectric sheet 212 provides separation between adjacent pairs ofelectrode sheets 206 to reduce electrical, inductive, or capacitanceinterference.

In some implementations, a desired thickness of the outer dielectricsheets is at least 0.5 μm, and preferably at least 1 μm or at least 10μm, while the inner dielectric sheets are at most 50 nm, 20 nm, or 10 nmthick. As noted above, an accurately controlled inner dielectric sheetthickness can ordinarily improve the reliable and reproducibleattachment of certain molecules to the pairs of electrode sheets 206.This in turn can result in more accurate readings from the sensor 200since it is less likely that other types of molecules inadvertentlyattach to the electrode sheets.

A groove or gap 210 in the inner dielectric sheet 208 can facilitate theattachment of a molecule 10 for analysis during operation. In someimplementations, a partial air gap can be introduced by localizedetching or by deposition with local masking to form a groove 210 in theinner dielectric sheet 208. For example, a 5 to 15 nm space can beetched to facilitate the attachment of certain biomolecules.

FIG. 13 is a flowchart for a manufacturing process of the molecularsensor 200 of FIG. 12 according to another embodiment. As shown in FIG.13, blocks 1302 to 1312 are collectively performed to form a stack thatis later sliced in block 1314 to form multiple chips that are attachedto a substrate in block 1316.

In block 1302, a first outer dielectric layer is provided, and a firstelectrode layer is deposited on the first outer dielectric layer inblock 1304. The first electrode layer can be deposited using a standardCMOS deposition technique. In some implementations, the outer dielectriclayer may have a different thickness than other outer dielectric layersto, for example, facilitate packaging of the sensor in a larger array ofsensors or to provide a greater exterior insulation. In otherimplementations, the thickness of the first outer dielectric layer maybe the same as other outer dielectric layers located between electrodesheets in the pairs of electrode sheets.

In block 1306, an inner dielectric layer is deposited on the firstelectrode layer. A second electrode layer is deposited on the innerdielectric layer in block 1308 to form a pair of electrode layers withthe inner dielectric layer between the first and second electrode layer.In block 1310, a second outer dielectric layer is deposited on thesecond electrode layer deposited in block 1308. The thickness of thesecond outer dielectric layer may be the same or may differ from thethickness of the first outer dielectric layer provided in block 1302.

In block 1312, it is determined whether a final number of pairs ofelectrode layers has been reached for the stack. If so, the processproceeds to block 1314 to slice through the stack at least once at anangle to the layers in the stack to form a plurality of chips from thesliced portions of the stack. On the other hand, if it is determinedthat the final number of pairs of electrode layers has not been reachedin block 1312, the process returns to block 1304 to deposit anotherfirst electrode layer on the second outer dielectric layer deposited inblock 1310. The depositing of the first electrode layer, the innerdielectric layer, the second electrode layer, and the second outerdielectric layer in blocks 1304 to 1310 repeats until a final number ofpairs of electrode layers has been reached in block 1312.

FIG. 14A provides an example of a stack 230 formed by performing blocks1302 to 1312 in the manufacturing process of FIG. 13. As shown in FIG.14A, a first outer dielectric layer 227 is provided and a firstelectrode layer 205 is deposited on the first outer dielectric layer227. An inner dielectric layer 209 is deposited on the first electrodelayer 205 and a second electrode layer 219 is deposited on the innerdielectric layer 209. A second outer dielectric layer 223 is depositedon the second electrode layer 219. This pattern of depositing a firstelectrode layer 205, an inner dielectric layer 209, a second electrodelayer 219, and a second dielectric layer 223 is repeated two more timesin the example of FIG. 14A to result in a stack 230 with three pairs ofelectrode layers.

In some implementations, a thin adhesion enhancing layer may bedeposited at the interfaces between the electrode layers and the innerdielectric layers to improve the adhesion of the layers. In one example,a 1 to 5 nm thick film material is deposited at the interface using amaterial such as Ti, Cr, Al, Zr. Mo, Nb, Ta, or Hf.

In some implementations, the electrode layers 205 and 219 are depositedwith a thickness of 1 to 40 nm or 5 to 15 nm. In such implementations,the inner dielectric layers 209 can be deposited with a similarthickness of 1 to 40 nm or 2 to 15 nm, but the outer dielectric layers223 are deposited with a thickness between 50 to 2,000 nm that is atleast one order of magnitude greater than the thickness of the innerdielectric layers 209.

Returning to the process of FIG. 13, the stack formed in blocks 1302 to1312, is sliced through at least once in block 1314 to form a pluralityof chips from the sliced portions of the stack. The stack is sliced atan angle to the layers in the stack to expose a cross section of thelayers deposited in the stack. In some implementations, the stack issliced at a 90 degree angle to the layers in the stack. In otherimplementations, the stack may be sliced at a different angle to thelayers in the stack.

FIG. 14B illustrates the slicing of the stack 230 of FIG. 14A to form aplurality of chips 232 including at least one pair of electrode sheets.As shown in FIG. 14B, the stack 230 is sliced along planes 225 to formthree chips 232, which may have the same thickness/height or differentthicknesses/heights.

In block 1316 of FIG. 13, the plurality of chips are attached to asubstrate so that the sliced portions of the first electrode layer orlayers and the second electrode layer or layers form a plurality ofpairs of electrode sheets at an angle to a substrate plane defined bythe substrate. In addition, the sliced portions of the inner dielectriclayer or layers form a plurality of inner dielectric sheets with eachinner dielectric sheet between each electrode sheet in each pair ofelectrode sheets.

The manufacturing process of FIG. 13 may be followed with one or moreadditional processes, such as with the performance of one or blocks inFIG. 6 discussed above. Such additional processes can include, forexample, forming a groove on an exposed end portion of each innerdielectric sheet (e.g., block 602 in FIG. 6), defining a gap in a coverlayer (e.g., block 604), roughening an exposed edge of each electrodesheet (e.g., block 606), depositing a gate electrode (e.g., block 608),forming a plurality of channels (e.g., block 610), and connecting leadconductors (e.g., block 612).

FIG. 14C is a cross section view showing the placement of a chip 232from FIG. 14B on a substrate 202 during the manufacturing process ofFIG. 13. As shown in FIG. 14C, a chip 232 has been rotated 90 degreesand attached to substrate 202 to reveal multiple exposed electrode sheetpairs 206. Each pair of electrode sheets 206 includes a first electrodesheet 207 and a second electrode sheet 215, with an inner dielectricsheet 208 sandwiched between the electrode sheets. Outer dielectricsheets 212 are provided between each pair of electrode sheets 206 and onthe ends of the chip 232. In some implementations the first or the lastouter dielectric sheets 212 may have a different thickness than otherouter dielectric sheets.

FIG. 15 illustrates the placement of multiple chips 232 on a substrate202 according to an embodiment. Adding more chips 232 to the substrate202 increases the number of pairs of electrode sheets, which in turn,provides more sites for attaching molecules to the exposed ends of theelectrode sheets. In the example of FIG. 15, the chips 232 are mountedon the substrate 202 with space between the chips 232. The spacesbetween the chips 232 in some implementations can be filled with apotting material such as SiO₂ paste or a precursor to SiO₂, such as HSQresist, which may be later planarized to reveal the top edges of theelectrode sheets using, for example, CMP polishing, FIB etching, or PMMAor HSQ filling and etching back by RIE.

Although the example of FIG. 15 shows chips each having three pairs ofelectrode sheets 206, other implementations may include a differentnumber of pairs of electrode sheets, such as chips having 2 to 2,000pairs of electrode sheets. Each electrode sheet can have a thickness of2 to 100 nm. In this regard, some implementations may include electrodesheets having a thickness of 1 to 40 nm or 5 to 15 nm, depending ondesign considerations such as the molecule to be analyzed.

FIG. 16 illustrates the placement of a dielectric cover layer 216 on themultiple chips 232 of FIG. 15 according to an embodiment. As shown inFIG. 16, the dielectric cover layer 216 can ordinarily facilitate theattachment of only a single molecule to the exposed portions of theelectrode sheets in an electrode sheet pair 206 in the gap 218. Asdiscussed above with reference to the example of FIGS. 7A and 7B, a maskline can be deposited and then removed after the dielectric cover layerhas been deposited to form the gap 218. In other implementations, thegap 218 may be formed by using a patterning process such as e-beamlithography or nano-imprinting, and etching an unmasked region to formthe gap 218. In some examples, the gap can have a width between 2 to 40nm or 5 to 15 nm to facilitate the attachment of a single molecule ateach pair of electrode sheets 206.

In addition, and as discussed above with reference to block 602 in FIG.6 and to grooves 210 in FIG. 12, an unmasked region of the innerdielectric sheets 208 can be, for example, etched by RIE, sputter etch,or a chemical etch like HF etch to form grooves 210 between theelectrode sheets in the electrode sheet pairs 206.

FIG. 17 is a top view of a molecular sensor with multiple chips 232 anddiverging lead conductors 220 according to an embodiment. As shown inFIG. 17, each lead conductor 220 diverges in width as the lead conductorextends away from an edge of the electrode sheet toward the contact 222.The lead conductors can be made of a conductive material such as goldfor carrying a test signal from the electrode sheets. In someimplementations, the thickness of the electrode sheets can be as smallas only 10 nm.

The lead conductors may then fan out from a width of approximately 10 nmto a scale of micrometers to allow for soldering at the contacts 222.The contacts 222 can include a contact pad array for circuit packaging,solder bonding, or wire bonding. In addition, a dielectric cover layer224 is deposited so that only an end portion of the electrode sheets areexposed for attaching a single molecule to each pair of electrode sheets206.

In some implementations, a gate electrode, such as the gate electrodes126 or 127 shown in FIG. 10 discussed above may also be applied to themolecular sensor to improve the accuracy of readings from the pairs ofelectrode sheets 206 by imposing an electric field to regulate thecharge carriers between the first electrode sheet 207 and the secondelectrode sheet 215, which serve as source and drain electrodes.

FIG. 18 is a top view of a molecular sensor with channels forintroducing a fluid to pairs of electrode sheets according to anembodiment. In the example of FIG. 18, each chip 232 provides a separatechannel with a group of pairs of electrode sheets 206, separated by awall 228. A fluid such as a gas or liquid containing the molecules to betested can then be introduced into the channel so that multiple pairs ofelectrode sheets can be used to test the molecules in the fluid. In FIG.18, each channel is loaded with a fluid containing a different DNAnucleobase for detection via the pairs of electrode sheets 206 in thechannel.

The arrangement shown in FIG. 18 can ordinarily allow for errorcorrection or compensation by loading the same fluid to be tested (e.g.,a fluid with molecules 10, 12, 14, or 16 in FIG. 18) across multiplepairs of electrode sheets 206 and using the different measurements forthe different pairs of electrode sheets to average out any error and/oreliminate a measurement that deviates by more than a threshold. Althoughthree pairs of electrode sheets are shown per channel in the example ofFIG. 18, a different number of pairs can be used in differentimplementations, such as ten or twenty pairs of electrode sheets perchannel.

In some implementations, the arrangement shown in FIG. 18 can includeone or more dielectric cover layers similar to the dielectric coverlayer 124 in FIG. 9 discussed above. The dielectric cover layer orlayers can be deposited at an angle to or perpendicular to the electrodesheets on the surface of the chips 232 to expose only a narrow gapportion of the electrode sheets for molecular sensing.

The molecular sensor devices and fabrication methods discussed aboveprovide numerous unique advantages that are not provided by previousmolecular sensors and fabrication methods. For example, the molecularsensors disclosed above do not require nano-fabrication, positioning,and adhesion of conductive islands. Conventional molecular sensorstypically include a pair of thin film electrodes facing each other in ahorizontally linear configuration, with a conductive island (e.g., agold island of 3 to 10 nm) that is transported and placed at a specificlocation on each electrode, or nano-pattern fabricated on eachelectrode. The size, adhesion strength, and positioning of suchconductive islands can critically affect the performance, reliability,and yield of such conventional molecular sensors, especially in the caseof genome sequencing. In some cases, the conductive islands may evenfall off of the electrodes.

In contrast, the molecular sensors disclosed above do not requirenano-fabrication, adhesion, or precise positioning of conductiveislands. As a result, the problems associated with the variability ofconductive island size, positioning, and adhesion strength are generallyavoided.

As another example advantage, the arrangement of electrode sheetsdiscussed above ordinarily allows for a much higher electricalconductance as compared to previous thin film sensor devices. Thishigher electrical conductance can provide an improved signal-to-noiseratio.

As yet another advantage, the disclosed processes and molecular sensorsprovide better control of the size of the exposed area for attachment ofa molecule on the electrodes themselves. As discussed above, the use ofcover layers can accurately control the size of the location formolecule attachment, which can help ensure that only a single moleculeattaches to the exposed area. The foregoing processes also provide amore accurate control of the dielectric layer thickness between theelectrodes, which can facilitate a higher device yield.

As yet another advantage, the fabrication processes disclosed aboveprovide an easier and lower cost over conventional fabrication processesfor molecular sensors. The multilayer deposition and planarizationprocesses discussed above can also allow for fabrication of thousands ormore massively parallel device arrays.

The foregoing description of the disclosed example embodiments isprovided to enable any person of ordinary skill in the art to make oruse the embodiments in the present disclosure. Various modifications tothese examples will be readily apparent to those of ordinary skill inthe art, and the principles disclosed herein may be applied to otherexamples without departing from the present disclosure. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive, and the scope of the disclosure is thereforeindicated by the following claims rather than by the foregoingdescription. All changes which come within the meaning and range ofequivalency of the claims are to be embraced within their scope.

What is claimed is:
 1. A method of manufacturing a molecular sensor, themethod comprising: forming a stack by at least: providing a first outerdielectric layer; depositing a first electrode layer on the first outerdielectric layer; depositing an inner dielectric layer on the firstelectrode layer; depositing a second electrode layer on the innerdielectric layer; and depositing a second outer dielectric layer on thesecond electrode layer; slicing through the stack at least once at anangle to the layers in the stack to form a plurality of chips from thesliced portions of the stack; and attaching the plurality of chips to asubstrate so that the sliced portions of the first electrode layer andthe second electrode layer form a plurality of pairs of electrode sheetsat an angle to a substrate plane defined by the substrate, and so thatthe sliced portions of the inner dielectric layer forms a plurality ofinner dielectric sheets with each inner dielectric sheet between eachelectrode sheet in each pair of electrode sheets.
 2. The method of claim1, wherein forming the stack further includes repeating the depositionof the first electrode layer, the inner dielectric layer, the secondelectrode layer, and the second outer dielectric layer at least once sothat each chip of the plurality of chips includes multiple pairs ofelectrode sheets.
 3. The method of claim 1, wherein the inner dielectriclayer has a first thickness and the second outer dielectric layer has asecond thickness at least one order of magnitude greater than the firstthickness.
 4. The method of claim 1, further comprising forming a groovelocated on an exposed end portion of each inner dielectric sheet.
 5. Themethod of claim 1, further comprising depositing a dielectric coverlayer at an angle or perpendicular to the plurality of pairs ofelectrode sheets opposite the substrate to define a gap exposing aportion of the plurality of pairs of electrode sheets.
 6. The method ofclaim 1, further comprising roughening an exposed edge of each electrodesheet.
 7. The method of claim 1, further comprising depositing a gateelectrode parallel to the substrate plane and perpendicular to anelectrode plane defined by an electrode sheet in the plurality of pairsof electrode sheets.
 8. The method of claim 1, further comprisingforming a plurality of channels, each channel arranged to introduce afluid to exposed portions of at least two pairs of electrode sheets ofthe plurality of pairs of electrode sheets.